https://scholars.lib.ntu.edu.tw/handle/123456789/640746
Title: | Studying the Roles of the Renin-Angiotensin System in Accelerating the Disease of High-Fat-Diet-Induced Diabetic Nephropathy in a db/db and ACE2 Double-Gene-Knockout Mouse Model | Authors: | Chen, Cheng-Yi Lin, Meng-Wei Xie, Xing-Yang Lin, Cheng-Han CHUNG WEI YANG Wu, Pei-Ching Liu, Dung-Huan Wu, Chih-Jen Lin, Chih-Sheng |
Keywords: | angiotensin converting enzyme II (ACE2); chymase; diabetic nephropathy; high-fat-diet; renin angiotensin system | Issue Date: | Jan-2024 | Journal Volume: | 25 | Journal Issue: | 1 | Source: | International journal of molecular sciences | Abstract: | Diabetic nephropathy (DN) is a crucial metabolic health problem. The renin-angiotensin system (RAS) is well known to play an important role in DN. Abnormal RAS activity can cause the over-accumulation of angiotensin II (Ang II). Angiotensin-converting enzyme inhibitor (ACEI) administration has been proposed as a therapy, but previous studies have also indicated that chymase, the enzyme that hydrolyzes angiotensin I to Ang II in an ACE-independent pathway, may play an important role in the progression of DN. Therefore, this study established a model of severe DN progression in a db/db and ACE2 KO mouse model (db and ACE2 double-gene-knockout mice) to explore the roles of RAS factors in DNA and changes in their activity after short-term (only 4 weeks) feeding of a high-fat diet (HFD) to 8-week-old mice. The results indicate that FD-fed db/db and ACE2 KO mice fed an HFD represent a good model for investigating the role of RAS in DN. An HFD promotes the activation of MAPK, including p-JNK and p-p38, as well as the RAS signaling pathway, leading to renal damage in mice. Blocking Ang II/AT1R could alleviate the progression of DN after administration of ACEI or chymase inhibitor (CI). Both ACE and chymase are highly involved in Ang II generation in HFD-induced DN; therefore, ACEI and CI are potential treatments for DN. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/640746 | ISSN: | 16616596 | DOI: | 10.3390/ijms25010329 |
Appears in Collections: | 醫學院附設醫院 (臺大醫院) |
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